Next-Generation Bioinformatics Approaches and Resources for Coronavirus Vaccine Discovery and Development—A Perspective Review

COVID-19 is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To fight this pandemic, which has caused a massive death toll around the globe, researchers are putting efforts into developing an effective vaccine against the pathogen. As genome sequencing projects for several coronavirus strains have been completed, a detailed investigation of the functions of the proteins and their 3D structures has gained increasing attention. These high throughput data are a valuable resource for accelerating the emerging field of immuno-informatics, which is primarily aimed toward the identification of potential antigenic epitopes in viral proteins that can be targeted for the development of a vaccine construct eliciting a high immune response. Bioinformatics platforms and various computational tools and databases are also essential for the identification of promising vaccine targets making the best use of genomic resources, for further experimental validation. The present review focuses on the various stages of the vaccine development process and the vaccines available for COVID-19. Additionally, recent advances in genomic platforms and publicly available bioinformatics resources in coronavirus vaccine discovery together with related immunoinformatics databases and advances in technology are discussed.

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Prediction of Physicochemical Properties of SARS-CoV-2 Protein in Bangladesh

10.31219/osf.io/usvg5 ◽

2020 ◽

Author(s):

Nilanjan Roy

Keyword(s):

Physicochemical Properties ◽

Development Process ◽

Vaccine Development ◽

Viral Proteins ◽

Instability Index ◽

Subunit Vaccines ◽

Grand Average ◽

Rapid Production ◽

Aliphatic Index ◽

Inactivated Vaccines

Awareness of the physicochemical properties of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is urgently required for the rapid production of live attenuated and inactivated vaccines. To develop subunit vaccines, it's also important to understand these properties for similar viral proteins. In this study, we predicted the physicochemical properties of SARS-CoV-2 protein that has been sequenced from Bangladeshi patients. Here we reported the number of amino acids, molecular weight, theoretical pI, amino acid composition, extinction coefficients, estimated half-life, instability index, aliphatic index, and grand average of hydropathicity of the SARS-CoV-2 protein in Bangladesh. As Bangladesh is consistently trying to contribute in the vaccine development process of SARS-CoV-2, we believe that this biocomputational study of physicochemical properties will give meaningful insights and will ease the way of vaccine development.

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Oral Peptide Vaccine against Hookworm Infection: Correlation of Antibody Titers with Protective Efficacy

Vaccines ◽

10.3390/vaccines9091034 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1034

Author(s):

Ahmed O. Shalash ◽

Luke Becker ◽

Jieru Yang ◽

Paul Giacomin ◽

Mark Pearson ◽

...

Keyword(s):

Immune Response ◽

Worm Burden ◽

Vaccine Development ◽

Protective Efficacy ◽

Digestive Enzyme ◽

Peptide Vaccine ◽

Effective Vaccine ◽

Antigen Delivery ◽

Hookworm Infection ◽

Linear Arrangement

Approximately 0.4 billion individuals worldwide are infected with hookworm. An effective vaccine is needed to not only improve the health of those affected and at high risk, but also to improve economic growth in disease-endemic areas. An ideal anti-hookworm therapeutic strategy for mass administration is a stable and orally administered vaccine. Oral vaccines are advantageous as they negate the need for trained medical staff for administration and do not require strict sterility conditions. Vaccination, therefore, can be carried out at a significantly reduced cost. One of the most promising current antigenic targets for hookworm vaccine development is the aspartic protease digestive enzyme (APR-1). Antibody-mediated neutralization of APR-1 deprives the worm of nourishment, leading to reduced worm burdens in vaccinated hosts. Previously, we demonstrated that, when incorporated into vaccine delivery systems, the APR-1-derived p3 epitope (TSLIAGPKAQVEAIQKYIGAEL) was able to greatly reduce worm burdens (≥90%) in BALB/c mice; however, multiple, large doses of the vaccine were required. Here, we investigated a variety of p3-antigen conjugates to optimize antigen delivery and establish immune response/protective efficacy relationships. We synthesized, purified, and characterized four p3 peptide-based vaccine candidates with: (a) lipidic (lipid core peptide (LCP)); (b) classical polymeric (polymethylacrylate (PMA)); and (c) novel polymeric (polyleucine in a branched or linear arrangement, BL10 or LL10, respectively) groups as self-adjuvanting moieties. BL10 and LL10 induced the highest serum anti-p3 and anti-APR-1 IgG titers. Upon challenge with rodent hookworms, the highest significant reduction in worm burden was observed in mice immunized with LL10. APR-1-specific serum IgG titers correlated with worm burden reduction. Thus, we provide the first vaccine-triggered immune response-protection relationship for hookworm infection.

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Identification of Highly Conserved SARS-CoV-2 Antigenic Epitopes with Wide Coverage Using Reverse Vaccinology Approach

Viruses ◽

10.3390/v13050787 ◽

2021 ◽

Vol 13 (5) ◽

pp. 787

Author(s):

Yasmin Hisham ◽

Yaqoub Ashhab ◽

Sang-Hyun Hwang ◽

Dong-Eun Kim

Keyword(s):

Amino Acid ◽

In Silico ◽

Vaccine Development ◽

Emerging Infectious Diseases ◽

Vaccination Strategy ◽

Viral Proteins ◽

Reverse Vaccinology ◽

Effective Vaccine ◽

Amino Acid Substitutions ◽

Time Required

One of the most effective strategies for eliminating new and emerging infectious diseases is effective immunization. The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) warrants the need for a maximum coverage vaccine. Moreover, mutations that arise within the virus have a significant impact on the vaccination strategy. Here, we built a comprehensive in silico workflow pipeline to identify B-cell- and T-cell-stimulating antigens of SARS-CoV-2 viral proteins. Our in silico reverse vaccinology (RV) approach consisted of two parts: (1) analysis of the selected viral proteins based on annotated cellular location, antigenicity, allele coverage, epitope density, and mutation density and (2) analysis of the various aspects of the epitopes, including antigenicity, allele coverage, IFN-γ induction, toxicity, host homology, and site mutational density. After performing a mutation analysis based on the contemporary mutational amino acid substitutions observed in the viral variants, 13 potential epitopes were selected as subunit vaccine candidates. Despite mutational amino acid substitutions, most epitope sequences were predicted to retain immunogenicity without toxicity and host homology. Our RV approach using an in silico pipeline may potentially reduce the time required for effective vaccine development and can be applicable for vaccine development for other pathogenic diseases as well.

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Characterization of Mucosal Immune Responses to Enterotoxigenic Escherichia coli Vaccine Antigens in a Human Challenge Model: Response Profiles after Primary Infection and Homologous Rechallenge with Strain H10407

Clinical and Vaccine Immunology ◽

10.1128/cvi.00617-15 ◽

2015 ◽

Vol 23 (1) ◽

pp. 55-64 ◽

Cited By ~ 20

Author(s):

Subhra Chakraborty ◽

Clayton Harro ◽

Barbara DeNearing ◽

Malathi Ram ◽

Andrea Feller ◽

...

Keyword(s):

Escherichia Coli ◽

Immune Response ◽

Immune Responses ◽

Vaccine Development ◽

Lavage Fluid ◽

Antibody Responses ◽

Enterotoxigenic Escherichia Coli ◽

Effective Vaccine ◽

Content Type ◽

Mucosal Immune Responses

ABSTRACTEnterotoxigenicEscherichia coli(ETEC) bacteria are the most common bacterial cause of diarrhea in children in resource-poor settings as well as in travelers. Although there are several approaches to develop an effective vaccine for ETEC, no licensed vaccines are currently available. A significant challenge to successful vaccine development is our poor understanding of the immune responses that correlate best with protection against ETEC illness. In this study, ETEC-specific mucosal immune responses were characterized and compared in subjects challenged with ETEC strain H10407 and in subjects rechallenged with the homologous organism. IgA responses to lipopolysaccharide (LPS), heat-labile toxin B subunit (LTB), and colonization factor antigen I (CFA/I) in antibody in lymphocyte supernatant (ALS), feces, lavage fluid, and saliva samples were evaluated. In all assay comparisons, ALS was the most sensitive indicator of a local immune response, but serum IgA was also a useful indirect marker of immune response to oral antigens. Volunteers challenged and then rechallenged with strain H10407 were protected from illness following rechallenge. Comparing mucosal antibody responses after primary and homologous rechallenge, protection against disease was reflected in reduced antibody responses to key ETEC antigens and in reduced fecal shedding of the H10407 challenge strain. Subjects challenged with strain H10407 mounted stronger antibody responses to LPS and LTB than subjects in the rechallenge group, while responses to CFA/I in the rechallenge group were higher than in the challenge group. We anticipate that this study will help provide an immunological benchmark for the evaluation of ETEC vaccines and immunization regimens in the future.

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Toll-Like Receptor and Cytokine Responses to Infection with Endogenous and Exogenous Koala Retrovirus, and Vaccination as a Control Strategy

Current Issues in Molecular Biology ◽

10.3390/cimb43010005 ◽

2021 ◽

Vol 43 (1) ◽

pp. 52-64

Author(s):

Mohammad Kayesh ◽

Md Hashem ◽

Kyoko Tsukiyama-Kohara

Keyword(s):

Immune Response ◽

Viral Infections ◽

Vaccine Development ◽

Effective Vaccine ◽

Therapeutic Tool ◽

Proper Understanding ◽

In Captivity ◽

In The Wild ◽

Koala Retrovirus ◽

Made In

Koala populations are currently declining and under threat from koala retrovirus (KoRV) infection both in the wild and in captivity. KoRV is assumed to cause immunosuppression and neoplastic diseases, favoring chlamydiosis in koalas. Currently, 10 KoRV subtypes have been identified, including an endogenous subtype (KoRV-A) and nine exogenous subtypes (KoRV-B to KoRV-J). The host’s immune response acts as a safeguard against pathogens. Therefore, a proper understanding of the immune response mechanisms against infection is of great importance for the host’s survival, as well as for the development of therapeutic and prophylactic interventions. A vaccine is an important protective as well as being a therapeutic tool against infectious disease, and several studies have shown promise for the development of an effective vaccine against KoRV. Moreover, CRISPR/Cas9-based genome editing has opened a new window for gene therapy, and it appears to be a potential therapeutic tool in many viral infections, which could also be investigated for the treatment of KoRV infection. Here, we discuss the recent advances made in the understanding of the immune response in KoRV infection, as well as the progress towards vaccine development against KoRV infection in koalas.

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Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.607198 ◽

2020 ◽

Vol 10 ◽

Author(s):

Marie-Noëlle Mévélec ◽

Zineb Lakhrif ◽

Isabelle Dimier-Poisson

Keyword(s):

Immune Response ◽

Molecular Mechanisms ◽

Vaccine Development ◽

Host Immune Response ◽

Oral Route ◽

Effective Vaccine ◽

Naked Dna ◽

Protection Mechanisms ◽

Immunogenic Proteins ◽

Cellular Immune

Toxoplasmosis is a parasitic disease affecting human, livestock and cat. Prophylactic strategies would be ideal to prevent infection. In a One Health vaccination approach, the objectives would be the prevention of congenital disease in both women and livestock, prevention/reduction of T. gondii tissue cysts in food-producing animals; and oocyst shedding in cats. Over the last few years, an explosion of strategies for vaccine development, especially due to the development of genetic-engineering technologies has emerged. The field of vaccinology has been exploring safer vaccines by the generation of recombinant immunogenic proteins, naked DNA vaccines, and viral/bacterial recombinants vectors. These strategies based on single- or few antigens, are less efficacious than recombinant live-attenuated, mostly tachyzoite T. gondii vaccine candidates. Reflections on the development of an anti-Toxoplasma vaccine must focus not only on the appropriate route of administration, capable of inducing efficient immune response, but also on the choice of the antigen (s) of interest and the associated delivery systems. To answer these questions, the choice of the animal model is essential. If mice helped in understanding the protection mechanisms, the data obtained cannot be directly transposed to humans, livestock and cats. Moreover, effectiveness vaccines should elicit strong and protective humoral and cellular immune responses at both local and systemic levels against the different stages of the parasite. Finally, challenge protocols should use the oral route, major natural route of infection, either by feeding tissue cysts or oocysts from different T. gondii strains. Effective Toxoplasma vaccines depend on our understanding of the (1) protective host immune response during T. gondii invasion and infection in the different hosts, (2) manipulation and modulation of host immune response to ensure survival of the parasites able to evade and subvert host immunity, (3) molecular mechanisms that define specific stage development. This review presents an overview of the key limitations for the development of an effective vaccine and highlights the contributions made by recent studies on the mechanisms behind stage switching to offer interesting perspectives for vaccine development.

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HIV-1 Accessory Proteins: Which one is Potentially Effective in Diagnosis and Vaccine Development?

Protein and Peptide Letters ◽

10.2174/0929866528999201231213610 ◽

2020 ◽

Vol 28 ◽

Author(s):

Alireza Milani ◽

Kazem Baesi ◽

Elnaz Agi ◽

Ghazal Marouf ◽

Maryam Ahmadi ◽

...

Keyword(s):

Immune Response ◽

Vaccine Development ◽

Treated Group ◽

Vaccine Antigen ◽

Accessory Proteins ◽

Serological Method ◽

Th2 Immune Response ◽

Untreated Individuals ◽

Immunogenic Properties ◽

Hiv 1

Background:: The combination antiretroviral therapy (cART) could increase the number of circulating naive CD4 T lymphocytes, but was not able to eradicate human immunodeficiency virus-1 (HIV-1) infection. Objective:: Thus, induction of strong immune responses is important for control of HIV-1 infection. Furthermore, a simple and perfect serological method is required to detect virus in untreated-, treated- and drug resistant- HIV-1 infected individuals. Methods:: This study was conducted to assess and compare immunogenic properties of Nef, Vif, Vpr and Vpu accessory proteins as an antigen candidate in mice and their diagnostic importance in human as a biomarker. Results:: Our data showed that in mice, all heterologous prime/ boost regimens were more potent than homologous prime/ boost regimens in eliciting Th1 response and Granzyme B secretion as CTL activity. Moreover, the Nef, Vpu and Vif proteins could significantly increase Th1 immune response. In contrast, the Vpr protein could considerably induce Th2 immune response. On the other hand, among four accessory proteins, HIV-1 Vpu could significantly detect treated group from untreated group as a possible biomarker in human. Conclusion:: Generally, among accessory proteins, Nef, Vpu and Vif antigens were potentially more suitable vaccine antigen candidates than Vpr antigen. Human antibodies against all these proteins were higher in HIV-1 different groups than healthy group. Among them, Vpu was known as a potent antigen in diagnosis of treated from untreated individuals. The potency of accessory proteins as an antigen candidate in an animal model and a human cohort study are underway.

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The Immune Correlates of Orthohantavirus Vaccine

Vaccines ◽

10.3390/vaccines9050518 ◽

2021 ◽

Vol 9 (5) ◽

pp. 518

Author(s):

Joon-Yong Bae ◽

Jin Il Kim ◽

Mee Sook Park ◽

Gee Eun Lee ◽

Heedo Park ◽

...

Keyword(s):

Vaccine Development ◽

Zoonotic Transmission ◽

Effective Vaccine ◽

Pandemic Preparedness ◽

Relative Paucity ◽

Immune Correlates ◽

Current Vaccine ◽

Pros And Cons ◽

Human Infections ◽

Sense Of Urgency

Zoonotic transmission of orthohantaviruses from rodent reservoirs to humans has been the cause of severe fatalities. Human infections are reported worldwide, but vaccines have been approved only in China and Korea. Orthohantavirus vaccine development has been pursued with no sense of urgency due to the relative paucity of cases in countries outside China and Korea. However, the orthohantaviruses continuously evolve in hosts and thus the current vaccine may not work as well against some variants. Therefore, a more effective vaccine should be prepared against the orthohantaviruses. In this review, we discuss the issues caused by the orthohantavirus vaccine. Given the pros and cons of the orthohantavirus vaccine, we suggest strategies for the development of better vaccines in terms of pandemic preparedness.

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Strategies for Vaccination: Conventional Vaccine Approaches Versus New-Generation Strategies in Combination with Adjuvants

Pharmaceutics ◽

10.3390/pharmaceutics13020140 ◽

2021 ◽

Vol 13 (2) ◽

pp. 140

Author(s):

Abdellatif Bouazzaoui ◽

Ahmed A. H. Abdellatif ◽

Faisal A. Al-Allaf ◽

Neda M. Bogari ◽

Saied Al-Dehlawi ◽

...

Keyword(s):

Viral Vectors ◽

Protein Production ◽

Vaccine Development ◽

Effective Vaccine ◽

The Novel ◽

Research Teams ◽

Advantages And Disadvantages ◽

Rapid Spread ◽

New Generation ◽

Conventional Vaccine

The current COVID-19 pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has raised significant economic, social, and psychological concerns. The rapid spread of the virus, coupled with the absence of vaccines and antiviral treatments for SARS-CoV-2, has galvanized a major global endeavor to develop effective vaccines. Within a matter of just a few months of the initial outbreak, research teams worldwide, adopting a range of different strategies, embarked on a quest to develop effective vaccine that could be effectively used to suppress this virulent pathogen. In this review, we describe conventional approaches to vaccine development, including strategies employing proteins, peptides, and attenuated or inactivated pathogens in combination with adjuvants (including genetic adjuvants). We also present details of the novel strategies that were adopted by different research groups to successfully transfer recombinantly expressed antigens while using viral vectors (adenoviral and retroviral) and non-viral delivery systems, and how recently developed methods have been applied in order to produce vaccines that are based on mRNA, self-amplifying RNA (saRNA), and trans-amplifying RNA (taRNA). Moreover, we discuss the methods that are being used to enhance mRNA stability and protein production, the advantages and disadvantages of different methods, and the challenges that are encountered during the development of effective vaccines.

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The Koala Immune Response to Chlamydial Infection and Vaccine Development—Advancing Our Immunological Understanding

Animals ◽

10.3390/ani11020380 ◽

2021 ◽

Vol 11 (2) ◽

pp. 380

Author(s):

Bonnie L Quigley ◽

Peter Timms

Keyword(s):

Immune Response ◽

Chlamydial Infection ◽

Vaccine Development ◽

Interleukin 17 ◽

Phascolarctos Cinereus ◽

Post Vaccination ◽

Research Systems ◽

Cytokine Levels ◽

Nucleic Acid Assay ◽

Immunological Research

Chlamydia is a significant pathogen for many species, including the much-loved Australian marsupial, the koala (Phascolarctos cinereus). To combat this situation, focused research has gone into the development and refinement of a chlamydial vaccine for koalas. The foundation of this process has involved characterising the immune response of koalas to both natural chlamydial infection as well as vaccination. From parallels in human and mouse research, it is well-established that an effective anti-chlamydial response will involve a balance of cell-mediated Th1 responses involving interferon-gamma (IFN-γ), humoral Th2 responses involving systemic IgG and mucosal IgA, and inflammatory Th17 responses involving interleukin 17 (IL-17) and neutrophils. Characterisation of koalas with chlamydial disease has shown increased expression within all three of these major immunological pathways and monitoring of koalas’ post-vaccination has detected further enhancements to these key pathways. These findings offer optimism that a chlamydial vaccine for wider distribution to koalas is not far off. Recent advances in marsupial genetic knowledge and general nucleic acid assay technology have moved koala immunological research a step closer to other mammalian research systems. However, koala-specific reagents to directly assay cytokine levels and cell-surface markers are still needed to progress our understanding of koala immunology.

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